What side effects are associated with this type of intervention?

The treatments for Phosphomannomutase 2 Deficiency (PMM2-CDG) include D-galactose, extended-release sialic acid, N-acetylmannosamine (ManNAc), and butyrate. Common side effects of these treatments can include gastrointestinal disturbances, such as diarrhea and constipation, as well as potential metabolic imbalances. For treatments similar to Epalrestat, which is an Aldose Reductase Inhibitor, side effects may include gastrointestinal issues, liver enzyme abnormalities, and hypersensitivity reactions. It is important to monitor patients closely for these adverse effects during treatment.

What prior FDA approvals exist?

There are no specific FDA-approved treatments for Phosphomannomutase 2 Deficiency (PMM2-CDG) mentioned in the provided context. However, treatments under investigation include oral epalrestat therapy, which is an aldose reductase inhibitor. Other therapies being explored for different congenital disorders of glycosylation (CDGs) include D-galactose supplementation and sialic acid derivatives, which aim to address various metabolic and clinical symptoms associated with these disorders.

What other types of research exist?

Promising novel alternatives to Epalrestat for PMM2-CDG patients include gene therapy approaches and enzyme replacement therapies. These treatments aim to address the underlying genetic and enzymatic deficiencies more directly. Additionally, small molecule therapies that can enhance residual enzyme activity or stabilize the defective enzyme are also being explored.

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Aldose Reductase Inhibitor

Epalrestat for PMM2-CDG

Phase 3

Waitlist Available

Led By Eva Morava-Kozicz, MD, PhD

Research Sponsored by Eva Morava-Kozicz

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥ 2 and < 18 years

Diagnosis of PMM2-CDG, based on molecularly confirmed biallelic PMM2 pathogenic variants (can be historical diagnosis with lab report on file)

Must not have

Hepatic impairment defined as any one of the following: AST/ALT >5x ULN in the 6 months prior to screening, Bilirubin >2X ULN in the last 6 months prior to screening, Synthetic liver dysfunction (albumin deficiency < 2.8 mmol/L) at screening, or Diagnosis of liver fibrosis (Fibroscan > 7 kPa) confirmed by liver elastogram at screening

Renal impairment defined as serum creatinine: > 0.5 mg/dL (≤ 6 years), > 0.7 mg/dL (7-10 years), > 1.24 mg/dL (≥ 11 years)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 9 months

Awards & highlights

Pivotal Trial

Summary

This trial is testing a medication called epalrestat, taken by mouth, to see if it helps children with a rare genetic disorder called PMM2-CDG. The goal is to check if the medication is safe and if it improves their metabolism and overall health. Researchers will compare the results to ensure the findings are accurate.

Who is the study for?

This trial is for children aged 2 to under 18 with PMM2-CDG, a rare genetic disorder. They must be able to follow the study plan and not be pregnant or at risk of pregnancy without proper contraception. Kids can't join if they're allergic to epalrestat, have anemia, kidney problems, low platelets, liver issues, other CDGs or are on certain other drugs.

What is being tested?

The study tests oral Epalrestat against a placebo in kids with PMM2-CDG. It's designed to see if it's safe and tolerable and whether it improves their condition. Participants will randomly receive either the drug or placebo without knowing which one they get.

What are the potential side effects?

While specific side effects for this trial aren't listed, common ones from similar trials may include allergic reactions to medication ingredients and potential impacts on blood sugar levels due to Epalrestat’s mechanism of action.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 2 and 17 years old.

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I have been diagnosed with PMM2-CDG based on genetic testing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had liver problems, like high enzyme levels or liver stiffness, in the last 6 months.

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My kidney function is impaired based on my age-specific creatinine levels.

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I have or might have a congenital disorder of glycosylation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 9 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~9 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 9 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Antithrombin III (ATIII)

Change in ICARS

Change in sorbitol (mmol/mol creatinine)

Secondary study objectives

Change in Nijmegen Pediatric CDG Rating Scale (NPCRS) score

Change of Body Max Index (BMI) percentile

Change of factor XI activity percentage

+3 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: EpalrestatExperimental Treatment1 Intervention

Epalrestat will be administered orally, 3 times per day (TID) spaced out as evenly as possible over 24 hours in a divided dose starting on Day 1 of the Study.

Group II: PlaceboPlacebo Group1 Intervention

Placebo will be administered orally, 3 times per day (TID) spaced out as evenly as possible over 24 hours in a divided dose starting on Day 1 of the Study.

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Phosphomannomutase 2 Deficiency (PMM2-CDG) is a congenital disorder of glycosylation that affects multiple systems due to defective glycoprotein synthesis. Treatments aim to correct the underlying metabolic defects. Epalrestat, an Aldose Reductase Inhibitor, works by reducing the accumulation of sorbitol, which can mitigate cellular stress and improve metabolic function. This is relevant for PMM2-CDG patients as it may help alleviate some symptoms by improving cellular homeostasis and reducing the burden of metabolic imbalances. Other treatments focus on dietary supplements like mannose or galactose to bypass the defective enzymatic steps, thereby improving glycosylation and overall cellular function.

Drug-Drug Interaction of the Sodium Glucose Co-Transporter 2 Inhibitors with Statins and Myopathy: A Disproportionality Analysis Using Adverse Events Reporting Data.